Optimum dose of neostigmine at two levels of atracurium-induced neuromuscular block

There is controversy about the optimum dose of neostigmine forantagonizing neuromuscular block. We have studied 57 patientsundergoing gynaecological surgery to establish a dose-responserelationship when neostigmine was given to antagonize atracurium-inducedblock. Anaesthesia was induced with thiopentone and fentanyland maintained with nitrous oxide and enflurane in oxygen andneuromuscular block was produced with a bolus of atracurium0.5 mg kg–1. At the time of antagonism of block, threegroups received neostigmine 20, 40 or 80 µg kg–1at 5–10% recovery of the compound muscle action potentialof the adductor pollicis (profound block) and three groups receivedone of these doses at 40–50% neuromuscular recovery (lightblock). At profound block, antagonism was prolonged by reducingthe dose of neostigmine from 40 µg kg–1 to 20 µgkg–1, but not shortened by increasing the dose from 40µg kg–1 to 80 µg kg–1. At light block,there was no significant difference between the three groupsin the time taken to reach a train-of-four ratio of 0.7. Therewas little benefit in increasing the dose of neostigmine from40 µg kg–1 to 80 µg kg–1 when antagonizingprofound neuromuscular block. When light block was antagonized,neostigmine 20 µg kg–1 was the optimum dose. Wesuggest that smaller doses of neostigmine than are given commonlyproduce adequate antagonism of atracurium-induced neuromuscularblock. (Br. J. Anaesth. 1994; 72: 82–85)     

Intraoperative reversal of neuromuscular block with sugammadex or neostigmine during extreme lateral interbody fusion, a novel technique for spine surgery

Purpose  

Extreme lateral interbody fusion (XLIF) is a method for stabilization of the lumbar spine. Intraoperatively, the surgeon identifies the lumbar nerve roots with a stimulator to prevent their injury. The objective of this study was to determine the extent to which shallow rocuronium-induced neuromuscular block must be intraoperatively reversed for reliable identification of nerve roots.     

Unmasked residual neuromuscular block after administration of vecuronium for days

IMPLICATIONS: Significant neuromuscular block may be present in patients who have received vecuronium for days.     

Normalization of acceleromyographic train-of-four ratio by baseline value for detecting residual neuromuscular block

Background. This study was designed to recognize the importanceof normalizing postoperative acceleromyographic train-of-four(TOF) ratio by the baseline TOF value obtained before neuromuscularblock for ensuring adequate recovery of neuromuscular function. Methods. In 120 patients, TOF responses of the adductor pollicisto the ulnar nerve stimulation were monitored by acceleromyography(AMG) during anaesthesia using propofol, fentanyl and nitrousoxide. Control TOF stimuli were administered for 30 min. A TOFratio measured at the end of control stimulation was regardedas a baseline value. Neuromuscular block was induced with vecuronium0.1 mg kg^–1 and was allowed to recover spontaneously.Duration to a TOF ratio of 0.9 as calculated by AMG (DUR-raw0.9) was compared with that of 0.9 as corrected by the baselineTOF ratio (i.e. 0.9xbaseline TOF ratio; DUR-real 0.9). Results. Baseline TOF ratios ranged from 0.95 to 1.47. The averageTOF ratios observed every 5 min were constant throughout controlstimulation from at time zero mean (SD) [range]; 1.11 (0.09)[0.94–1.42] to at 30 min 1.13 (0.11) [0.95–1.47].The DUR-real 0.9 was 91.0 (18.0) [51.3–131.0] min andwas significantly longer than the DUR-raw 0.9 (81.2 (16.3) [41.3–123.0]min). Conclusions. Baseline TOF ratios measured by AMG are usuallymore than 1.0 and vary widely among patients. Therefore a TOFratio of 0.9 displayed postoperatively on AMG does not alwaysrepresent adequate recovery of neuromuscular function and shouldbe normalized by baseline value to reliably detect residualparalysis.     

Twitch tension and train-of-four ratio during prolonged neuromuscular monitoring at different peripheral temperatures

In eight healthy patients, the influence of the train-of-four (TOF) response of prolonged neuromuscular monitoring and of different peripheral temperatures was studied during normal core temperature. Anaesthesia was induced and maintained with midazolam-fentanyl and a 70/30% mixture of nitrous oxide and oxygen. The mechanical TOF response of the adductor pollicis muscle (twitch tension and TOF ratio), was recorded simultaneously in both hands using supramaximal TOF stimulation of the ulnar nerve at the wrist. One arm was kept normothermic. The other arm was cooled using cold infusions and cold packings. Skin, muscle and core temperatures were continuously measured. In the normothermic arm (skin temperature greater than 32.0 degrees C), the twitch tension and TOF ratio were unchanged following 130-230 min of continuous nerve stimulation. In the hypothermic arm the twitch tension and TOF ratio showed only minor variations above a skin temperature of 32.0 degrees C (corresponding to a mean muscle temperature of 34.5 +/- 0.3 degrees C). Below a skin temperature of 32.0 degrees C a progressive decrease in TOF response was recorded. A linear relationship was found between skin temperature and TOF response as well as between muscle temperature and TOF response. At a skin temperature of 27.0 degrees C (corresponding to a mean muscle temperature of 30.8 +/- 0.4 degrees C), an approximate 20% reduction in twitch tension and a 10% decrease in TOF ratio were recorded with a considerable interindividual variation. We conclude that prolonged TOF nerve stimulation does not change the mechanical twitch response in patients with a normal central and peripheral temperature. A peripheral skin temperature below 32.0 degrees C with sustained and normal body temperature is, however, associated with changes in both twitch tension and TOF ratio that may be a source of error when evaluating neuromuscular function.     

Recovery characteristics of patients receiving either sugammadex or neostigmine and glycopyrrolate for reversal of neuromuscular block: a randomised controlled trial

Sugammadex more rapidly and reliably reverses rocuronium‐induced neuromuscular block compared with neostigmine, but it is not known if subsequent patient outcomes, including nausea, vomiting and other aspects of recovery are modified. In this study, we compared the recovery characteristics of sugammadex and neostigmine/glycopyrrolate following reversal of neuromuscular block. This was a single‐centre, randomised, blinded, parallel‐group clinical trial in women undergoing elective day‐surgical laparoscopic gynaecological surgery, with a standardised general anaesthesia regimen that included rocuronium. Neuromuscular block was reversed with either sugammadex 2 mg.kg^?1 or neostigmine 40 μg.kg^?1 and glycopyrrolate 400 μg. The primary outcome was the incidence of nausea and vomiting during the first six postoperative hours. Secondary outcomes included other measures of postoperative recovery such as patient symptoms and recovery scores. Three‐hundred and four women were analysed by intention‐to‐treat (sugammadex n = 151, neostigmine n = 153), which included four major protocol violations. There was no significant difference between sugammadex and neostigmine groups in the incidence of early nausea and vomiting (49.0% vs. 51.0%, respectively; OR 0.92, 95%CI 0.59–1.45; p = 0.731). Double vision (11.5% vs. 20.0%; p = 0.044) and dry mouth (71.6% vs. 85.5%; p = 0.003) were less common after sugammadex. Sedation scores at 2 h were also lower after sugammadex (median (IQR [range]) 0 (0‐3 [0‐10]) vs. 2 (0‐4.[0‐10]); p = 0.021). Twenty‐four‐hour recovery scores were not significantly different between groups. Reversal with sugammadex in this patient population did not reduce postoperative nausea or vomiting compared with neostigmine/glycopyrrolate.     

Twitch augmentation and train-of-four fade during onset of neuromuscular block after subclinical doses of suxamethonium

We have studied the train-of-four (TOF) response mechanomyographically during onset of neuromuscular block produced by subclinical doses of suxamethonium in order to follow the augmentation of the first twitch of the TOF (T1) and TOF fade compared with control TOF responses before the drug was given. In the groups given suxamethonium 0.05, 0.1, 0.2 and 0.3 mg kg-1, the increments in T1 after administration of the drug were observed before twitch depression occurred; these were mean 22.3 (SEM 8.1)%, 19.2 (3.3)%, 10.8 (2.0)% and 4.2 (2.2)%, respectively. This effect was more marked with the lower doses (P < 0.05). The degree of TOF fade was moderate during onset of neuromuscular block and depended on the dose of drug. The results of this study suggest that low doses of suxamethonium produced transient increase in muscle tension and twitch depression with significant TOF fade. We conclude that suxamethonium was associated with presynaptic effects as a consequence of brief stimulation of acetylcholine release followed by progressive diminution at the neuromuscular junction.      

Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium-induced neuromuscular block

Study Objective: (1) To determine the time to peak effect of neostigmine (time to peak antagonism) during atracurium- or vecuronium-induced neuromuscular block; and (2) to determine the effect on time to peak effect of neostigmine during atracurium-induced neuromuscular block, when the dose of neostigmine is increased from 35 μg/kg to 70 μg/kg.

Design: Prospective, randomized clinical study.

Setting: Gynecologic operating room suite at a university hospital.

Patients: 45 ASA I and II women admitted for gynecologic laparotomy.

Interventions: Anesthesia was performed with thiopental sodium, fentanyl, halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF) stimulation and mechanomyography were used to monitor neuromuscular transmission. Neostigmine was administered while a constant degree of neuromuscular block was maintained at a twitch height at a point between 4% and 11% of the control twitch height, using a continuous infusion of atracurium or vecuronium. The patients were randomized to three groups, with 15 patients in each group. Group 1 received atracurium block antagonized with neostigmine 35 μg/kg; group 2 received vecuronium block antagonized with neostigmine 35 μg/kg; and group 3 received atracurium block antagonized with neostigmine 70 μg/kg.

Measurements and Main Results: The degree of neuromuscular block at antagonism was similar in the three groups. Time to peak effect (mean ± SD) on TOF ratio was significantly longer in Group 1 (9.7 ± 3.0 minutes) versus Group 2 (6.6 ± 1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium-induced block was reduced from 9.7 ± 3.0 minutes to 6.3 ± 2.0 minutes when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3 compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2.

Conclusion: The time to peak effect of neostigmine 35 μg/kg is about 6 to 10 minutes when antagonizing a constant degree of atracurium- or vecuronium-induced neuromuscular block at a twitch height at a point between 4% and 11%. Even though the time to peak effect was longer with atracurium than with vecuronium, clinically significant differences between the antagonizing effect of atracurium versus vecuronium block were not demonstrated. The time to peak effect during atracurium-induced block decreased when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg.     

Effect of antagonizing residual neuromuscular block by neostigmine and atropine on postoperative vomiting

Eighty patients undergoing outpatient surgery under generalanaesthesia were allocated randomly to two groups: in groupA residual neuromuscular block was antagonized with a mixtureof neostigmine 1.5 mg and atropine 0.5 mg; in group B spontaneousrecovery was allowed. The patients were assessed after operationin hospital and 24 h after discharge. We found a significantdifference (P<0.05) in requirements for antiemetic therapywith a smaller need in the group which received neostigmine(in group A four of 40 patients received an antiemetic comparedwith 12 in group B). There was no significant difference infrequency of nausea or vomiting between the two groups. Theincidence of postoperative nausea was 14 in group A and 18 ingroup B and the number of patients with postoperative vomitingwas 10 in group A and 15 in group B.     

Perioperative monitoring of neuromuscular transmission using acceleromyography prevents residual neuromuscular block following pancuronium

The frequency of postoperative residual neuromuscular block following the use of the long-acting non-depolarizing muscle relaxants is high, and manual evaluation of the response to nerve stimulation does not eliminate the problem. In this prospective and randomized study we evaluated the hypothesis that perioperative use of acceleromyography would allow for a more rational and precise administration of the long-acting muscle relaxant pancuronium resulting in a decrease in 1) the incidence and severity of postoperative residual neuromuscular block, 2) the amount of pancuronium used, and 3) the time from end of surgery to tracheal extubation. Forty adult patients were randomized into two groups, one managed without the use of a nerve stimulator, the other monitored using train-of-four (TOF) nerve stimulation and acceleromyography. All patients were anaesthetized with diazepam, fentanyl, thiopenione, nitrous oxide, and in some patients halothane, and they all received pancuronium 0.08–0.1 mg kg^-1 for tracheal intubation, and 1–2 mg for maintenance of neuromuscular block. Neostigmine 2.5 mg preceded by atropine 1 mg was administered for reversal. In the patients managed without a nerve stimulator, the trachea was extubated when the anaesthetist judged the neuromuscular function to have recovered adequately for upper airway protection and spontaneous ventilation. In patients monitored with acceleromyography, the trachea was extubaled when the TOF ratio was above 0.70. In all 40 patients, TOF ratio was measured using mechanomyography immediately after tracheal extubation and the patients were evaluated for clinical signs of residual neuromuscular block. Train-of-four ratios, as measured mechanically, varied between 0.26 and 0.96 (median 0.65) in the group not monitored dunng the operation with acceleromyography. Seven patients in this group were unable to sustain head lift for 5 seconds and five patients were unable to lift an arm to the opposite shoulder, as compared to 1 and 0 patients, respectively, in the group monitored using acceleromyography (P<0.05). The lime from end of surgery to tracheal extubation varied between 0 and 25 min (median 10 min) in the group not monitored as compared to 7–47 min (median 15 min) in the monitored group (P<0.01). There was no statistically significant difference in the total dose of pancuronium given in the two groups. It is concluded, that by using acceleromyography during Anaesthesia it is possible to avoid the problem of residual neuromuscular block following pancuronium. However, in this study this happened at the expense of a slightly prolonged recovery time (5 min longer). Under the conditions of the study the use of acceleromyography did not influence the amount of pancuronium used during anaesthesia.     

Recovery characteristics after early administration of anticholinesterases during intense mivacurium-induced neuromuscular block

The time course of recovery after early administration of anticholinesterasesduring intense mivacurium-induced block was evaluated by recordingthe mechanomyographic response of the adductor pollicis to post-tetaniccount (PTC) and train-of-four (TOF) ulnar nerve stimulation.Seventy-two adult patients receiving thiopentone, fentanyl,nitrous oxide, isoflurane anaesthesia and mivacurium 0.15 mgkg^–1 were allocated randomly to one of six equal groupsaccording to the type of anticholinesterase and intensity ofblock at which antagonism was attempted. Groups 1, 3 and 5 receivedneostigmine 0.07 mg kg^–1, while groups 2, 4 and 6 receivededrophonium 1 mg kg^–1. At the time of administration ofantagonist there was no response to PTC in groups 1 and 2, aPTC of 1 or more was detectable in groups 3 and 4 and the firsttwitch of the TOF (T1) had recovered to 10% in the conventionalantagonism groups (5 and 6). The longest clinical duration (CD)values (time from administration of mivacurium to T1 25%) wereencountered in groups 1, 5 and 6 and were 17.4 (7.9), 19.7 (3.4)and 21.4 (4.8) min, respectively. CD was reduced significantlyin groups 2, 3 and 4 and values were 13.9 (3.5), 13.7 (3.5)and 13.8 (3.3) min, respectively. Recovery indices (Rl) (timeinterval between T1 25% and 75%) were 13.8 (7.3), 6.3 (1.4),4.6 (1.8), 6.0 (2.1), 3.7 (2.2) and 4.8 (3.1) min in groups1–6, respectively and was prolonged with neostigmine antagonismat PTC 0 (group 1). Reversal time (RT) (time between administrationof antagonist and TOF 0.70) was 34.9 (16.6) min in group 1 whoreceived neostigmine at PTC 0 and was prolonged markedly comparedwith all other groups. Antagonism with edrophonium at PTC 0(group 2) was associated with an RT of 16.7 (5.1) min and wassignificantly longer compared with the conventional antagonismgroups only. Reversal times were similar in groups 3–6.Total recovery times (TRT) (time between administration of mivacuriumand TOF 0.70) were 41.5 (16.6), 23.2 (5.2), 23.2 (5.3), 24.1(4.5), 26.8 (4.8) and 28.5 (9.1) min in groups 1–6, respectively,and was markedly prolonged in group 1 only. In summary, administrationof neostigmine during intense mivacurium block, not responsiveto TOF and PTC stimulation was associated with marked delayin recovery, possibly because of inhibition of plasma cholinesterase.At this intensity of block, edrophonium was preferable. It isadvisable to wait for a detectable PTC before attempting antagonismof an intense mivacurium block. After detection of PTC, neostigmineor edrophonium antagonism reduced the clinical duration butnot the total recovery time compared with conventional reversaladministered at T1 10%.